Publications by authors named "N Skelton"
Article Synopsis
- BamA is a crucial part of the β-barrel assembly machine (BAM) that helps insert proteins into the outer membrane of Gram-negative bacteria like E. coli.
- Researchers used in vitro selection techniques to find peptide macrocycles that can disrupt BamA's function by binding to different conformational states, specifically Peptide Targeting BamA-1 (PTB1) and Peptide Targeting BamA-2 (PTB2).
- These findings are important for developing new antibiotics targeting BamA and could also be applied to discover modulators for other similar proteins in the future.
Unlabelled: Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA and RNA, and their regulatory roles in translation, signal transduction, and cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step in guanine nucleotide biosynthesis executed by inosine-5´-monophosphate dehydrogenase (IMPDH). MPA is used clinically as an immunosuppressant, but whether inhibition of bacterial IMPDH (GuaB) is a valid antibacterial strategy is controversial.
View Article and Find Full Text PDFThe Structural Genomics Consortium is an international open science research organization with a focus on accelerating early-stage drug discovery, namely hit discovery and optimization. We, as many others, believe that artificial intelligence (AI) is poised to be a main accelerator in the field. The question is then how to best benefit from recent advances in AI and how to generate, format and disseminate data to enable future breakthroughs in AI-guided drug discovery.
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- Researchers focused on inhibiting Cbl-b, a protein that regulates T cell activation, to explore its therapeutic potential.
- After screening a vast DNA-encoded library, they identified a promising compound that was confirmed through biochemical assays.
- Optimization efforts were enhanced by obtaining a cocrystal structure, revealing how the compound binds to the SH2 domain of Cbl-b, although its effectiveness in cells was limited to high concentrations.
Autophagy-related proteins (Atgs) drive the lysosome-mediated degradation pathway, autophagy, to enable the clearance of dysfunctional cellular components and maintain homeostasis. In humans, this process is driven by the mammalian Atg8 (mAtg8) family of proteins comprising the LC3 and GABARAP subfamilies. The mAtg8 proteins play essential roles in the formation and maturation of autophagosomes and the capture of specific cargo through binding to the conserved LC3-interacting region (LIR) sequence within target proteins.
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